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Beyond cell shape: A novel role for the bacterial actin MreB in chemotaxis

超越细胞形状：细菌肌动蛋白 MreB 在趋化性中的新作用

基本信息

批准号：
10653302
负责人：
RANDY M MORGENSTEIN
金额：
$ 43.72万
依托单位：
OKLAHOMA STATE UNIVERSITY STILLWATER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-12-01 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10653302
关键词：
Actins Affect Alanine Alleles Anabolism Anti-Bacterial Agents Antibiotic Resistance Antibiotics Bacteria Bacterial Physiology Biochemical Biological Assay Biology Biophysics Cell Death Cell Shape Cell Survival Cell Wall Cell physiology Cells Cellular biology Chemotaxis Cysteine Cysteine Metabolism Pathway Cytoskeleton Data Development Eukaryotic Cell Evolution Flagella Genes Genetic Goals Growth Homologous Gene Image Analysis Immune system Infection Knowledge Lead Learning Libraries Maintenance Measures Messenger RNA Microbial Physiology Microbiology Microscopy Modification Molecular Mutagenesis Mutation Pharmaceutical Preparations Physiological Physiology Play Polymers Proteins Proteomics Regulation Regulation of Cell Shape Regulon Research Resistance Rod Role Scanning Shapes Sulfur Sulfur Metabolism Pathway Suppressor Mutations Swimming System Techniques Time Transfer RNA Virulence Work cell growth cell motility cysteine-tRNA depolymerization design experimental study fitness insight molecular dynamics mutant novel novel therapeutics pathogen protein complex quantitative imaging therapy development tool transcriptome sequencing transcriptomics

项目摘要

Project Summary/Abstract The cytoskeleton is important for proper physiology in both eukaryotic and bacterial cells. However, unlike eukaryotic cells, for which much work has been done to determine the role of the cytoskeleton in cellular physiology, there has been very little work on this aspect of bacterial cell biology. Disruption of the cytoskeleton often leads to cell shape changes and cell death. The major actin homolog in bacteria is MreB and it is thought to be essential for rod shape. The goal of this work is to remove this black box of microbiology and determine the role of the cytoskeleton in microbial physiology. A deeper understanding of MreB’s function and bacterial physiology can guide the development of novel antibacterial therapies, as well as provide insight into the evolution of the cytoskeleton. Disrupting basic physiology will make it difficult for infections to take hold in the body, giving the host’s natural defenses time to clear the infection. This proposal will focus on the role of MreB in cell shape regulation, growth, and chemotaxis. To understand how MreB functions we will take a systematic approach MreB using a combination of genetic, biophysical, and microscopy techniques to building and analyzing an alanine-scanning mutagenesis library of MreB mutants that have replaced the native allele. We will analyze the effect of these mutations on multiple aspects of cell shape and look for suppressor mutations to loss of cell shape. We will screen this library for the effects on chemotaxis to determine domains of MreB that interact with the chemotaxis machinery. All together this research will determine the role of the bacterial cytoskeleton in bacterial chemotaxis, cell shape, and growth. These insights will provide a starting point for the development of novel therapeutics that can be used to stop or slow infections, giving the host immune system time to clear the infection. Additionally, many pathogens use flagella-based motility to increase their virulence. Learning more about how chemotaxis works will enable us to develop therapies that can inhibit motility in the host, lessening infection. To the best of our knowledge, this study will be the first to take a systematic approach to understanding MreB biology.

项目总结/摘要细胞骨架对于真核生物和细菌的正常生理都是重要的细胞然而，不像真核细胞，已经做了很多工作，确定细胞骨架在细胞生理学中的作用，在细菌细胞生物学方面的研究。细胞骨架的破坏通常会导致细胞形状改变和细胞死亡。细菌中主要的肌动蛋白同源物是MreB，被认为是棒形所必需的。这项工作的目标是去除微生物学的黑盒子，微生物生理学中的细胞骨架。更深入地了解MreB的功能细菌生理学可以指导新型抗菌疗法的发展，也为细胞骨架的进化提供了新的视角。扰乱基本生理机能这将使感染难以在体内扎根，使宿主的自然是时候清除感染了该提案将重点关注MreB在细胞中的作用，形状调节、生长和趋化性。为了理解MreB的功能，我们将采用一种系统化的方法，遗传学、生物物理学和显微镜技术相结合，分析已取代的MreB突变体的丙氨酸扫描诱变文库，原生等位基因我们将分析这些突变对细胞多个方面的影响，形状和寻找抑制突变的细胞形状的损失。我们将筛选这个图书馆对于对趋化性的影响，以确定MreB的结构域，趋化机制总之，这项研究将确定细菌细胞骨架在细菌中的作用。趋化性、细胞形状和生长。这些见解将提供一个起点，开发新的治疗方法，可用于阻止或减缓感染，宿主免疫系统清除感染的时间。此外，许多病原体使用鞭毛为基础的运动，以增加其毒力。了解更多关于趋化性这项工作将使我们能够开发出能够抑制宿主运动的疗法，感染据我们所知，这项研究将是第一次采取系统的了解MreB生物学的方法。